Elevated Levels of Circulating miR-92a Are Associated with Impaired Glucose Homeostasis in Patients with Obesity and Correlate with Metabolic Status After Bariatric Surgery
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miRNAs are small non-coding RNAs, some of which are expressed in adipose tissues, are present in the circulation, and are regulated in obesity. Bariatric surgery (BS) has been proposed to lead to activation of brown adipose tissue, an effect that may be related to beneficial effects of BS on systemic metabolism. Here, we evaluated circulating levels of miR-92a and miR-99b, two miRNAs proposed as biomarkers of brown fat activity, in a cohort of patients with severe obesity before and after BS, and studied their potential relationship with BS-associated improvements in metabolic parameters.
Circulating levels of miR-92a and miR-99b were quantified in a cohort of 26 patients (age, 48 ± 10 years; BMI, 45 ± 7 kg/m2) before and 6 months after BS. Clinical parameters were determined at different time points and correlations among them were studied.
Basal levels of miR-92a were significantly increased in patients with obesity relative to lean controls. Serum miR-92a levels were strongly reduced at 6 months after BS, reaching levels similar to those in controls. Serum miR-99b levels were unchanged in relation to both the obese condition and BS. Elevated levels of miR-92a were directly correlated with worsened glucose homeostasis parameters and poor BS outcome.
Our findings show that miR-92a is elevated in conditions of obesity, and its reduction after BS correlates with metabolic improvement. Further studies would be necessary to establish miR-92a as serum biomarker and potential predictor of the BS success in improving the metabolic status of patients with obesity.
KeywordsmiR-92a miR-99b Obesity Bariatric surgery Brown adipose tissue
We thank the IGTP High Content Genomics and Bioinformatics Core facility and staff (Lauro Sumoy, PhD, and Raquel Pluvinet, PhD) for their contribution to this publication.
DS-I is an Investigator of the Miguel Servet Fund from Carlos III National Institute of Health, Spain. This study was supported by the Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, by the Fondo Europeo de Desarrollo Regional (FEDER), Madrid, Spain (FIS17/01455 and SAF2017-85722R), and by the K-sted 651010-Project number 70084900-analyze number M50676 from Norwegian University of Science and Technology (NTNU). DJP was supported by a grant from the Spanish Ministry of Science and Innovation - MINECO (RYC-2014-16938).
Compliance with Ethical Standards
Samples from patients included in this study were provided by the IGTP HUGTP Biobank and the “Biobanc de l’Hospital Infantil Sant Joan de Déu per a la Investigació,” both integrated in the Spanish National Biobanks Network of Instituto de Salud Carlos III (PT13/0010/0009) and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committees.
Conflict of Interest
Francesc Villarroya reports grants from Ministerio de Ciencia, Innovació y Universidades, outside the submitted work. The other authors declare that they have no competing interests.
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